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Sodium butyrate attenuates liver fibrogenesis via promoting H4K8 crotonylation

Ruiqi Tang1, Hua Zha1, Rongrong Liu2

  • 1State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Rd., Hangzhou, 310003, China.

Molecular and Cellular Biochemistry
|April 3, 2025
PubMed

Insights

Sodium butyrate (NaB), a histone deacetylase inhibitor, shows promise for treating liver fibrosis. It improves liver function and reduces fibrosis by altering histone crotonylation, offering a novel therapeutic approach.

Area of Science:

  • Biochemistry
  • Hepatology
  • Molecular Biology

Background:

  • Liver fibrosis is a significant health concern.
  • Histone deacetylase (HDAC) inhibitors are being explored for therapeutic potential.
  • Dietary compounds like sodium butyrate (NaB) offer a unique avenue for investigation.

Purpose of the Study:

  • To investigate the therapeutic potential of sodium butyrate (NaB) in liver fibrosis.
  • To elucidate the mechanism of NaB's action through histone crotonylation.
  • To evaluate NaB's effects both in vitro and in vivo.

Main Methods:

  • In vitro studies using TGF-β-stimulated LX2 hepatic stellate cells.
  • In vivo studies using CCl4-induced liver fibrosis model in ICR mice.
  • Analysis of fibrotic markers, HDAC expression, and histone crotonylation (H4K8).

Main Results:

  • NaB inhibited LX2 cell growth and reduced fibrotic markers (ACTA2, COL1A1) dose-dependently.
  • NaB treatment improved liver function and suppressed fibrosis in mice.
  • NaB inhibited Hdac2/Hdac3, increasing H4K8 crotonylation and modulating fibrosis-related genes.

Conclusions:

  • Sodium butyrate (NaB) demonstrates significant efficacy in ameliorating liver fibrosis.
  • NaB's mechanism involves HDAC inhibition and increased histone crotonylation.
  • NaB presents a promising therapeutic strategy for liver disease treatment.
Keywords:
H4K8 crotonylationHistone crotonylationHistone deacetylase inhibitionLiver fibrosisSodium butyrate

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